1995 Fiscal Year Final Research Report Summary
Research for the mechanism of bronchinal hyperresponsiveness
| Project/Area Number |
06670602
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | AKITA UNIVERSITY |
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Principal Investigator |
SHIOYA Takanobu Akita Univ Dep of Med Ass Professer, 医学部, 講師 (90170852)
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| Co-Investigator(Kenkyū-buntansha) |
KUROKAWA Hirokazu Akita Univ Dep of Med Instroctor, 医学部, 助手 (50234589)
SASAKI Masahiro Akita Univ Dep of Med Instroctor, 医学部, 助手 (20221278)
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| Project Period (FY) |
1994 – 1995
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| Keywords | bronchial hyperresponsiveness / bronchial asthma / neuropeptide / endothelin / muscarinic receptor / substance P / vagin newe / airway smooth muscle |
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| Research Abstract |
We have studied the effect of neurokinin A (NKA) on tracheal smooth muscle (TSM) contraction caused by administration of acetylcholine (ACh) intra-arterially (ia) into the tracheal circulation, or a bilateral stimulation of the vagus nerves in 26 mongrel dogs. As a result, substantial augmentation of tracheal contractile responses to 10^<-10>-10^<-7> molia ACh was obtained 10 min after administration of NKA (p<0.05). Significant potentiation of tracheal contractiion to vagal stimulation for 10-20 Hz was also observed after administration of 10^<-8> mol NKA (p<0.05). We have demonstrated a substantial contractile effect of NKA on canine tracheal smooth muscle that is not related to histamine release from respiratory mast cells. We have also demonstrated that NKA causes augmentation of the parasympathetic tracheal contractile response induced by ia administration of ACh and efferent vagus nerve stimulation. These data suggest that potentiation of vagal contractile response by NKA is related to post-synaptic activation of the parasympathetic nerves.
The effect of FK224 on isometric contraction of canine tracheal smooth muscle in situ was studied. Contraction was induced by administration of substance P,neurokinin A,and neurokinin B intra-arterially into the tracheal circulation in five mongrel dogs. FK224 inhibited substance P- and neurokinin A-induced contraction in a dose-dependent manner, but it did not inhibit neurokinin B-induced contraction significantly. These data suggest that FK224 is a sural antagonist of both neurokinin 1 andd neurokinin 2 receptors with a similar potency in in vivo experiments.
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[Publications] Shioya, T., Kagaya, M., Sano, M., Itaba, M., Fujii, T., and Niura, M.: "Effect of a new dual neurokinin antagonist on airway smooth muscle in situ." Arzneimittel Forschung. 45 (II). 1194-1197 (1995)
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[Publications] Shioya, T., Kagaya, M., Miura, S., Shindo, T., Sano, M., Miura, M.: "Effectiveness of an anti cholinergic agent in elderly patients with bron chial asthma." Arzneimitte Forschng. (in print). (1996)
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[Publications] Shioya, T., Kagaya, M., Sano, M., Itaba, M., Shindo, T., Miura, M.: "Bronchodilatory effect of trquizium bromide in patients with COPb" Eur.J.Clin Pharmacol. (in print). (1996)
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「研究成果報告書概要(欧文)」より
